Spinal Cord Injury

Central neuropathic pain in Women with Spinal Cord Injury. Central neuropathic pain develops in greater than 75% of both males and females suffering a spinal cord injury (SCI), and is particularly debilitating in veterans. Unfortunately, chronic neuropathic SCI pain severely impacts the quality of life of both SCI individuals and their caregivers, and is extremely difficult to manage. Analgesic drugs such as pregabalin are only partially effective in a small subset of patients. Our incomplete understanding of underlying mechanisms stalls the development of druggable targets for SCI pain. An important clue comes from the mounting evidence that intraspinal inflammation, specifically microglial activation, contributes to neuropathic pain following peripheral nerve injury, and this is sexually dimorphic. These studies suggest that sex differences may have masked the effectiveness of pharmacotherapeutics for neuropathic pain in earlier clinical trials. To address this question, in collaboration with multiple investigators within the Spinal Cord and Brain Injury Research Center at the University of Kentucky, the research group is using behavioral pharmacology and flow cytometry to examine the contribution of sex, spinal microglia, and peripheral inflammation to the development of SCI-induced pain, and investigating pioglitazone and rosiglitazone or other PPARγ agonists as new analgesics for women with SCI. Their new preliminary data suggest that PIO reduces pain in female mice at doses that are 100-1000 fold less than required to reduce pain in male mice. Since sexually dimorphic pain responses are being recognized across a variety of neuropathologies, development of effective immunomodulatory agents through the completion of their studies could have a broad impact in the fields of neuroscience and immunology.

Key publications:

Gollihue JL, Patel SP, Eldahan KC, Cox DH, Donahue RR, Taylor BK, Sullivan PG, Rabchevsky AG. Effects of Mitochondrial Transplantation on Bioenergetics, Cellular Incorporation, and Functional Recovery after Spinal Cord Injury. Journal of Neurotrauma. 35(15):1800-1818. (2018) PMID: 29648982.